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Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00302003
First received: March 9, 2006
Last updated: October 24, 2013
Last verified: October 2013

March 9, 2006
October 24, 2013
February 2006
March 2012   (final data collection date for primary outcome measure)
  • Minimum time to a requirement for involved-field radiotherapy (IFRT), requirement for additional chemotherapy and IFRT for retrieval, occurrence of a second malignant neoplasm, or death from any cause [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Minimum time to a relapse of higher risk at any time, any relapse following treatment with protocol-mandated IFRT, death from any cause, or the occurrence of a second malignant neoplasm [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Minimum time to a relapse of any kind, death from any cause, or occurrence of a second malignant neoplasm [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00302003 on ClinicalTrials.gov Archive Site
Time to death [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
Used to compute actuarial survival rate.
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma
A Phase III Study for the Treatment of Children and Adolescents With Newly Diagnosed Low Risk Hodgkin Disease

This phase III trial is studying how well combination chemotherapy works when given before radiation therapy and/or additional chemotherapy in treating young patients with newly diagnosed Hodgkin's lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving more than one drug (combination chemotherapy) and giving them together with radiation therapy may kill more cancer cells.

OBJECTIVES:

I. Investigate the paradigm of response-based therapy for low-risk Hodgkin's lymphoma by eliminating involved-field radiotherapy (IFRT) in patients who achieve a complete remission (CR) after initial chemotherapy.

II. Investigate whether 3 courses of doxorubicin hydrochloride, vincristine, prednisone, and cyclophosphamide (AV-PC) for the treatment of low-risk Hodgkin's lymphoma is sufficient to induce CR in at least 80% of patients.

III. Investigate whether patients who experience a low-risk relapse after initial treatment with chemotherapy alone can be successfully treated with a salvage regimen comprising ifosfamide and vinorelbine ditartrate with dexamethasone, etoposide phosphate, cisplatin, and cytarabine (IV/DECA) and IFRT.

IV. Maintain the overall survival for patients with low-risk Hodgkin's lymphoma at or above 97%.

V. Determine the prognostic significance of very early response as measured by fludeoxyglucose-positron emission tomography (FDG-PET) or gallium after the first course of chemotherapy.

VI. Evaluate the prognostic significance of elevation of erythrocyte sedimentation rate and C-reactive protein at the time of diagnosis in patients with low-risk Hodgkin's lymphoma on CR rate and relapse rate after chemotherapy alone.

VII. Determine the frequency and severity of late effects of therapy, including thyroid dysfunction, infertility, cardiotoxicity, and second malignant neoplasms.

OUTLINE: This is a multicenter study.

INITIAL CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (IV) over 10-30 minutes and cyclophosphamide IV over 1 hour on days 1-2, vincristine IV on days 1 and 8, prednisone orally (PO) on days 1-7, and filgrastim (G-CSF) subcutaneously (SC) on days 3-7 and 9-14. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients achieving complete remission (CR) proceed to observation. Patients achieving partial remission proceed to radiotherapy. Patients who have a low-risk relapse after achieving CR on initial chemotherapy proceed to salvage chemotherapy followed by radiotherapy. Patients who have stable disease or disease progression go off study.

SALVAGE CHEMOTHERAPY: Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1-5, and G-CSF SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients then receive dexamethasone IV over 15 minutes every 12 hours, etoposide phosphate IV over 3 hours every 12 hours, and cytarabine IV over 3 hours every 12 hours on days 1 and 2; cisplatin IV over 6 hours on day 1; and G-CSF SC or IV beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients then proceed to radiotherapy.

INVOLVED-FIELD RADIOTHERAPY (IFRT): Beginning 4 weeks after completion of chemotherapy, patients undergo IFRT once daily, 5 days a week, for 2.8 weeks. Patients who do not achieve CR go off study.

After completion of study treatment, patients are followed periodically for up to 10 years.

Interventional
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Childhood Favorable Prognosis Hodgkin Lymphoma
  • Childhood Lymphocyte Depletion Hodgkin Lymphoma
  • Childhood Mixed Cellularity Hodgkin Lymphoma
  • Childhood Nodular Sclerosis Hodgkin Lymphoma
  • Stage I Childhood Hodgkin Lymphoma
  • Stage II Childhood Hodgkin Lymphoma
  • Radiation: radiation therapy
    Undergo radiation therapy
    Other Names:
    • irradiation
    • radiotherapy
    • therapy, radiation
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Drug: prednisone
    Given orally
    Other Names:
    • DeCortin
    • Deltra
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: ifosfamide
    Given IV
    Other Names:
    • Cyfos
    • Holoxan
    • IFF
    • IFX
    • IPP
  • Drug: vinorelbine tartrate
    Given IV
    Other Names:
    • Eunades
    • navelbine ditartrate
    • NVB
    • VNB
  • Drug: dexamethasone
    Given IV
    Other Names:
    • Aeroseb-Dex
    • Decaderm
    • Decadron
    • DM
    • DXM
  • Drug: etoposide phosphate
    Given IV
    Other Names:
    • ETOP
    • Etopophos
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: cytarabine
    Given IV
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Biological: filgrastim
    Given IV or subcutaneously
    Other Names:
    • G-CSF
    • Neupogen
Experimental: Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
Treatment consists of 3 cycles of Doxorubicin hydrochloride IV (25 mg/m2) days 1 & 2, Vincristine sulfate IV (1.4 mg/m2 [max 2.8 mg]) Days 1 & 8, Prednisone orally (40 mg/m2) Days 1-7, Cyclophosphamide IV (600 mg/m2) Days 1 & 2, Filgrastim by mouth or IV (5 micrograms/kg/dose) 24 hours after Cyclophosphamide complete. See detailed description for remainder of therapy.
Interventions:
  • Radiation: radiation therapy
  • Drug: doxorubicin hydrochloride
  • Drug: vincristine sulfate
  • Drug: prednisone
  • Drug: cyclophosphamide
  • Drug: ifosfamide
  • Drug: vinorelbine tartrate
  • Drug: dexamethasone
  • Drug: etoposide phosphate
  • Drug: cisplatin
  • Drug: cytarabine
  • Biological: filgrastim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
287
Not Provided
March 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed Hodgkin's lymphoma meeting the following criteria:

    • Newly diagnosed disease
    • Stage IA OR stage IIA without bulky disease
    • No lymphocyte-predominant histology
  • Staging on this study will be determined by the clinical stage; surgical staging is strongly discouraged, except for the rare situation of equivocal imaging studies below the diaphragm
  • Patients may not have received any previous chemotherapy or radiation therapy; patients may not have received systemic corticosteroids within 30 days of enrollment on this protocol; steroids used for treatment of contrast agent allergy required for computed tomography (CT) scans are acceptable
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^3
  • Total bilirubin =< 1.5 x normal
  • Alanine (ALT) =< 2.5 x normal
  • Shortening fraction >= 27% by echocardiogram OR ejection fraction >= 50% by multi-gated acquisition (MUGA)
  • No pathologic prolongation of QTc interval on 12-lead electrocardiography (ECG)
  • Female patients of childbearing potential must have a negative pregnancy test
  • Lactating females must agree that they will not breastfeed a child while on this study
  • Fertile patients must use effective contraception
  • Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Both
up to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00302003
AHOD0431, NCI-2009-00377, CDR0000459962, U10CA098543, COG-AHOD0431
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Frank Keller Children's Oncology Group
Children's Oncology Group
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP